Copyright
©The Author(s) 2018.
World J Gastroenterol. Sep 7, 2018; 24(33): 3695-3708
Published online Sep 7, 2018. doi: 10.3748/wjg.v24.i33.3695
Published online Sep 7, 2018. doi: 10.3748/wjg.v24.i33.3695
Table 1 MicroRNA involved in hepatocellular carcinoma and their function in the hepatocyte growth factor/c-Met axis
miRNA | Functions | Effect of miR in HGF/c-Met axis | Levels in HCC | Ref. |
miR-34 | Cell invasion, proliferation | Inhibits c-Met | Downregulated | [83] |
miR-199 | Proliferation, cell motility, | Tumor-suppressor | Downregulated | [84] |
cell invasion | ||||
miR-340 | Cell invasion, cell migration | Inhibits c-Met | Downregulated | [85] |
miR-126 | Cell proliferation, | Inhibits c-Met | Downregulated | [86] |
cell invasion, inhibits angiogenesis | ||||
miR181-a | Cell motility and invasion | Inhibits c-Met | Upregulated | [87] |
let-7 family | Represses cell proliferation, invasion, metastasis and resistance therapy | Inhibits c-Met signaling downstream | Downregulated | [88,89] |
miR-148 | Promotes apoptosis, suppress cell invasion | Tumor-suppressor | Downregulated | [90] |
miR-1 | Cell migration, cell proliferation | Tumor-suppressor | Downregulated | [91] |
miR-26a | Cell proliferation, invasion, and migration | Inhibits c-Met signaling downstream | Downregulated | [92] |
miR-122 | Induces apoptosis | Inhibition of c-Met | Downregulated | [93] |
miR-145 | Cell viability, cell migration | Inhibits c-Met signaling downstream | Downregulated | [94] |
miR-449 | Promotes apoptosis, reduces proliferation | Decreases c-Met levels | Downregulated | [95] |
miR-200 | Cell migration and invasion | Decreases HGF-synthesis in fibroblasts | Upregulated | [96] |
miR-101 | Cell proliferation, migration and invasion | Inhibits c-Met signaling downstream | Downregulated | [97] |
Table 2 Compounds used in clinical trials to treat hepatocellular carcinoma patients
Agent | Targets | Phase | Activity | HCC stage | Ref. |
Sorafenib | Raf, MAPK, VEGFR, PDGFRβ | III | Anti-tumor | Advanced | [98] |
Anti-angiogenesis | |||||
Cabozanitinib | VEGFR2, KIT, RET, AXL | III | Anti-tumor | Advanced | [99] |
Brivanib | FGFR, VEGFR | II | Anti-angiogenesis | Advanced | [100] |
Foretinib | FLT1, PDGFRβ, c-Met, VEGFR-2, Tie-2 | II | Anti-tumor | Advanced | [101] |
FLT4, RON, FLT3, KIT | Anti-angiogenesis | ||||
Everolimus | mTOR | III | Anti-tumor | Advanced | [102] |
Cobazitinib | c-Met, VEGFR-2, RET | II | Anti-tumor | Advanced | [103] |
Anti-angiogenesis | |||||
Ramucirumab | VEGFR-2 | III | Anti-angiogenesis | Advanced | [104] |
MSC2156119J | c-Met | Ib/II | Anti-tumor, anti-mestastasis | Advanced | [105] |
Gefitinib | EGFR, c-Met, HGF, | II | Anti-tumor | Advanced | [106] |
Bevacizumab | VEGFRs | II | Anti-angiogenesis | Advanced | [107] |
AZD6244 | MEK1/2 | Ib | Anti-tumor | Advanced | [108] |
AZD4547 | p-FGFR-1, p-FGFR-2 | I | Anti-tumor, anti-angiogenesis | Advanced | [109] |
p-c-Met, | |||||
p-AKT, | |||||
p-ERK | |||||
MK2461 | c-Met, Ftl-1 | I | Anti-tumor | Advanced | [110] |
Crizotinib | p-c-Met | Ib | Anti-angiogenesis | Advanced | [111] |
ALK | |||||
Bortezomib | Proteasome inhibitor | II | Anti-tumor | Advanced | [102] |
Docetaxel | EGFR | II | Anti-tumor | Advanced | |
INC280 | p-c-Met | II | Anti-tumor | Advanced | [111] |
Table 3 List of compounds analyzed in laboratories that show potential anti-tumor properties against hepatocellular carcinoma
Agent | Target | Activity | Ref. |
LZ8 | Inhibits the expression of c-Met, ERK, AKT | Induces apoptosis | [112] |
Inhibits the phosphorylation of JNK, AKT, ERK, p-AKT | |||
Stabilizes p53 | |||
Damnacanthal | Inhibits the phosphorylation of c-Met | Inhibits cell proliferation and cell invasion | [113] |
Decreases MMP-2 activity | |||
GEN-203 | Inhibits the phosphorylation of c-Met | Blocks cell proliferation | [114] |
JNJ38877605 | Inhibits phosphorylation of c-Met | Induces apoptosis | [70] |
SRI31215 | Blocks pro-HGF activation | Inhibits cell proliferation | [70] |
Madecassoside | Inhibits the phosphorylation of ERK1/2 and | Blocks cell proliferation | [115] |
PKC | |||
PHA665752 | Inhibits phosphorylation of c-Met and FGFR | Blocks cell proliferation | [116] |
EPZ011989 | Inhibits histone methylation | Blocks cell proliferation | [82] |
YC-1 | Inhibits the DNA synthesis | Arrests cell cycle and induce apoptosis | [117] |
- Citation: García-Vilas JA, Medina MÁ. Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications. World J Gastroenterol 2018; 24(33): 3695-3708
- URL: https://www.wjgnet.com/1007-9327/full/v24/i33/3695.htm
- DOI: https://dx.doi.org/10.3748/wjg.v24.i33.3695